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An Update on Gene Therapy in Parkinson’s Disease

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Abstract

Gene therapy for Parkinson’s disease (PD) may offer an alternative to current pharmacologic and surgical treatments; the former are limited by motor complications and non-motor adverse effects, and both by lack of neuroprotection. Three main strategies under investigation using gene transfer for targeted protein expression include improving availability of dopamine to the striatum with more continuous delivery, reducing activity in the subthalamic nucleus by locally inducing γ-aminobutyric acid expression, or protecting and restoring nigrostriatal neuronal function with trophic factor expression. This review summarizes the components of gene therapy for PD, the preclinical rationale for each strategy, data from the most recently published clinical trials using four different vector-gene agents, and challenges in moving gene therapy forward. Thus far, safety data from phase 1 trials have been encouraging for all four agents and one phase 2 trial suggests modest symptomatic efficacy, but definitive conclusions on efficacy cannot yet be drawn.

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Disclosure

Conflicts of interest: J. Witt: has received grant support and travel support from Ceregene, Inc., and has received grant support from Medtronic, Inc.; W.J. Marks: has received grant support and travel support from Ceregene, Inc.; has been a consultant for Medtronic, Inc.; and has received honoraria and travel support from Medtronic, Inc.

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  1. Department of Neurology, University of California, San Francisco, UCSF Box 1838, 1635 Divisadero Street, Suite 520, San Francisco, CA, 94115, USA

    Jennifer Witt & William J. Marks Jr.

  2. Parkinson’s Disease Research, Education, and Clinical Center, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA

    Jennifer Witt & William J. Marks Jr.

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  1. Jennifer Witt
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Witt, J., Marks, W.J. An Update on Gene Therapy in Parkinson’s Disease. Curr Neurol Neurosci Rep 11, 362–370 (2011). https://doi.org/10.1007/s11910-011-0197-8

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